The long term objective of this proposal is to study the origin(s) and evolution of RNA virus systems via computer-based sequence analysis. RNA viruses are the major causative agents of human, animal and plant viral diseases. Knowledge of sequence relationships within RNA virus groups, between such groups and to potential cellular homologues is of primary interest in tracing the origins of viruses as well as elucidating mechanisms of emergence of new pathogenic strains. The use of computer-assisted comparisons of primary sequence data (nucleic acid or protein) is a powerful approach to questions of this nature. In addition, RNA viruses represent a highly divergent set of biologically related sequences and therefore provide a model database for development of new computer programs and strategies necessary for determining the most distant relationships between the genes of other organisms. Our specific aims are the following: 1) analysis of relationships between viruses known to utilize reverse transcriptase (RT) in their lifecycle and cellular elements with RT-like sequences; 2) quantitation of evolutionary relationships among picornaviruses and related plant viruses; and 3) development of computer-assisted methodologies for quantitation of the most distant protein sequence relationships.